This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this proposed study is to investigate small molecule natural product-derived hypoxia-inducible factor-1 (HIF-1) inhibitors as potential molecular-targeted agents for the treatment of neuroblastoma, the most common pediatric solid tumor predominantly found in early childhood. The Specific Aims are: 1) to determine the effects of natural product-derived HIF-1 inhibitors on hypoxia-induced dedifferentiation in neuroblastoma cells;and 2) to evaluate the potential of natural product-derived HIF-1 inhibitors to overcome hypoxia-induced resistance to chemotherapeutic agents.